ArticleMolecular medicine reports2018
Sterol uptake and sterol biosynthesis act coordinately to mediate antifungal resistance in Candida glabrata under azole and hypoxic stress.
Article in Molecular medicine reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
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- Spectrum of activity and mechanisms of azole-bisphosphonate synergy in pathogenicMicrobiology spectrum · 2024Article
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- Expression of ERG11, ERG3, MDR1 and CDR1 genes in Candida tropicalisBiomedica : revista del Instituto Nacional de Salud · 2023Article
- Redefining pleiotropic drug resistance in a pathogenic yeast: Pdr1 functions as a sensor of cellular stresses inmSphere · 2023Article
- Metal Nanoparticles to CombatMicroorganisms · 2023Review
- The performance of plant essential oils against lactic acid bacteria and adverse microorganisms in silage production.Frontiers in plant science · 2023Review
- Expression pattern of drug-resistance genes ERG11 and TAC1 in Candida albicans Clinical isolates.Molecular biology reports · 2022Article
- Investigation of the Defective Growth Pattern and Multidrug Resistance in a Clinical Isolate of Candida glabrata Using Whole-Genome Sequencing and Computational Biology Applications.Microbiology spectrum · 2022Article
- Molecular investigations onRSC advances · 2022Article
- Antifungal Activity of Fibrate-Based Compounds and Substituted Pyrroles That Inhibit the Enzyme 3-Hydroxy-methyl-glutaryl-CoA Reductase ofMicrobiology spectrum · 2022Article
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- Loss-of-FunctionmSphere · 2021Article
- Citronellal Exerts Its Antifungal Activity by Targeting Ergosterol Biosynthesis inJournal of fungi (Basel, Switzerland) · 2021Article
- Current and promising pharmacotherapeutic options for candidiasis.Expert opinion on pharmacotherapy · 2021Article
- Remodeling of theVaccines · 2020Article
- FTIR and Raman Spectroscopy-Based Biochemical Profiling Reflects Genomic Diversity of ClinicalInternational journal of molecular sciences · 2019Article
- Microevolution of the pathogenic yeastsMicrobial cell (Graz, Austria) · 2019Review
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Authors and funding
7 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Pathogenic fungi, including Candida glabrata, develop strategies to grow and survive both in vitro and in vivo under azole stress. However, the mechanisms by which yeast cells counteract the inhibitory effects of azoles are not completely understood. In the current study, it was demonstrated that the expression of the ergosterol biosynthetic genes ERG2, ERG3, ERG4, ERG10, and ERG11 was significantly upregulated in C. glabrata following fluconazole treatment. Inhibiting ergosterol biosynthesis using fluconazole also increased the expression of the sterol influx transporter AUS1 and the sterol metabolism regulators SUT1 and UPC2 in fungal cells. The microarray study quantified 35 genes with elevated mRNA levels, including AUS1, TIR3, UPC2, and 8 ERG genes, in a C. glabrata mutant strain lacking ERG1, indicating that sterol importing activity is increased to compensate for defective sterol biosynthesis in cells. Bioinformatic analyses further revealed that those differentially expressed genes were involved in multiple cellular processes and biological functions, such as sterol biosynthesis, lipid localization, and sterol transport. Finally, to assess whether sterol uptake affects yeast susceptibility to azoles, we generated a C. glabrata aus1∆ mutant strain. It was shown that loss of Aus1p in C. glabrata sensitized the pathogen to azoles and enhanced the efficacy of drug exposure under low oxygen tension. In contrast, the presence of exogenous cholesterol or ergosterol in medium rendered the C. glabrata AUS1 wild‑type strain highly resistant to fluconazole and voriconazole, suggesting that the sterol importing mechanism is augmented when ergosterol biosynthesis is suppressed in the cell, thus allowing C. glabrata to survive under azole pressure. On the basis of these results, it was concluded that sterol uptake and sterol biosynthesis may act coordinately and collaboratively to sustain growth and to mediate antifungal resistance in C. glabrata through dynamic gene expression in response to azole stress and environmental challenges.
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